Renal denervation modulates neurohormonal activity and inflammation in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) accounts for >50% of cases with heart failure (HF) and is often accompanied by derangements in several organs including kidney. Under normal conditions, the heart and kidney functions are reciprocally regulated by several bidirectional pathways that include neurohormonal, hemodynamic, and endocrine signaling, however, the underlying renal mechanisms during HFpEF remains largely unknown. Current evidence postulates that sympathetic nervous system (SNS) hyperactivation and low-grade inflammation play a key role in HFpEF, however, whether these mechanisms are cause or effect of HFpEF remains unknown. The kidney responds to volume overload in HFpEF via modulation of glomerular function, RAAS activation and norepinephrine release. Separately, selective denervation has been shown to reduce immune activation in hypertension, post myocardial infarction, and inflammatory arthritis, Therefore, the purpose of the study was to investigate whether renal denervation (RDN) in HFpEF modulates SNS activity thus RAAS, to reduce stress, and inflammation. Methods: C57BL/6J (WT, 50-52 wks) mice w/o and with HFpEF, and w/o and with RDN were used in the study. Aorto-vena cava fistula (AVF) was created as a model of diastolic dysfunction and serial ECHO was done to denote HFpEF (ejection fraction, EF > 50%). Results: AVF mice showed exercise intolerance, increased plasma catecholamines and low levels of atrial and brain natriuretic peptides (ANP and BNP resp.) but increased C-type natriuretic peptide (CNP) compared to WT groups. RDN improved exercise ability, increased ANP and BNP, and decreased plasma catecholamines in RDN+ AVF group. AVF hearts showed increased inflammatory cell infiltration and cytokine expression; RDN abrogated these changes. Further, RDN attenuated abnormal cardiac indices (Ejection fraction, fractional shortening, E/A ratio, and E/e’ ratio) and SNS activity following AVF. GFR was increased and renal resistive index (RI) decreased in RDN and RDN+AVF mice. In AVF mice, cardiac vasculature showed rarefaction and reduction of septal branches that improved following RDN. Conclusion: Taken together, our results suggest that RDN enhances cardiac regeneration by modulating SNS activity, improving renal function, and reduction of inflammation. NIH grant: DK116591, AR071789 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.